Inherited epidermolysis bullosa (EB) encompasses those diseases characterized by mechanically fragile skin and the tendency for blister formation. As of May 1998, four major types, at least 23 phenotypically distinctive subtypes, and at least 200 different genotypes have been described. Now that over 3,000 clinically well characterized patients with EB have been assembled via the National EB Registry, we propose to use the Registry, and the mechanism of a K24 Award, to attempt to address several clinically relevant and timely issues, to include (1) phenotype - genotype correlations across both major and minor types and subtypes of inherited EB, and the identification of those genotypes which have specific prognostic or therapeutic significance., (2) initiation of a prospective interventional clinical trial to assess the possible beneficial role of isotretinoin or another systemic retinoid as a chemopreventive agent against the development of additional squamous cell carcinomas in those patients with RDEB-HS who have developed at least one such tumor; (3) initiation of one or more other clinical trials to determine the benefit, if any, in the performance of selected medical or surgical interventions in groups of patients having more severe forms of EB, to include (a) early elective gastrostomy placement, (b) hand splinting, (c) use of one or more topical cytokine preparations and/or newer wound, healing dressings, (d) the use of topical or systemic antioxidant agents, and (e) aggressive nutritional supplementation; and (4) characterization of baseline metabolic and nutritional parameters in patients with severe generalized forms of inherited EB. It is hoped that the results of these several proposed clinical studies will provide new insights into the management of patients with EB, as well as provide an excellent means whereby young investigators interested in patient-oriented research can be mentored and trained.